11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy.

OBJECTIVE: The objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe). METHODS: Healthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle. RESULTS: Post-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min-1, p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015). CONCLUSIONS: Dynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.

Spatial heterogeneity in the response of the proximal femur to two lower-body resistance exercise regimens.

Understanding the skeletal effects of resistance exercise involves delineating the spatially heterogeneous response of bone to load distributions from different muscle contractions. Bone mineral density (BMD) analyses may obscure these patterns by averaging data from tissues with variable mechanoresponse. To assess the proximal femoral response to resistance exercise, we acquired pretraining and posttraining quantitative computed tomography (QCT) images in 22 subjects (25-55 years, 9 males, 13 females) performing two resistance exercises for 16 weeks. One group (SQDL, n = 7) performed 4 sets each of squats and deadlifts, a second group (ABADD, n = 8) performed 4 sets each of standing hip abductions and adductions, and a third group (COMBO, n = 7) performed two sets each of squat/deadlift and abduction/adduction exercise. Subjects exercised three times weekly, and the load was adjusted each session to maximum effort. We used voxel-based morphometry (VBM) to visualize BMD distributions. Hip strength computations used finite element modeling (FEM) with stance and fall loading conditions. We used QCT analysis for cortical and trabecular BMD, and cortical tissue volume. For muscle size and density, we analyzed the cross-sectional area (CSA) and mean Hounsfield unit (HU) in the hip extensor, flexor, abductor, and adductor muscle groups. Whereas SQDL increased vertebral BMD, femoral neck cortical BMD and volume, and stance hip strength, ABADD increased trochanteric cortical volume. The COMBO group showed no changes in any parameter. VBM showed different effects of ABADD and SQDL exercise, with the former causing focal changes of trochanteric cortical bone, and the latter showing diffuse changes in the femoral neck and head. ABADD exercise increased adductor CSA and HU, whereas SQDL exercise increased the hip extensor CSA and HU. In conclusion, we observed different proximal femoral bone and muscle tissue responses to SQDL and ABADD exercise. This study supports VBM and volumetric QCT (vQCT) to quantify the spatially heterogeneous effects of types of muscle contractions on bone.